LOS ANGELES — There’s no talking about his latest movie with director Steven Soderbergh. He’ll talk around it. He’ll talk you through his involvement with it. But he won’t talk about what actually happens on screen. He says he can’t, really.

“Side Effects,” opening Friday in Boston, is a psychological thriller set amid psychiatric offices and high-stakes pharmacology. There is a plot twist, then another, then, oops, Soderbergh has said too much already. The Oscar winner for 2000’s “Traffic” doesn’t want to give the quote that gives away a single one of the surprises in what he insists will be the last movie he makes, at least for some time.

“Here’s the problem,” Soderbergh says as a shrimp cocktail is delivered to the sofa where he is sitting in a high-end Beverly Hills hotel. “How do you sell a movie in which the best-case scenario for the audience is they know absolutely nothing? How do you convince people not to tell their readers anything? That’s the hard part.”

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Soderbergh’s friend and frequent collaborator, screenwriter Scott Z. Burns, is game to try. He says he loves movies where the rug gets pulled out from under the audience, and is hopeful reviewers and filmgoers will treat his latest with the same respect they showed “The Crying Game” or “The Usual Suspects.” But those movies came out in the early–to-mid-1990s, before everyone was on the Internet and entire TV networks were devoted to celebrity gossip.

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“I generally tell people: The best roller coaster rides go through familiar landscapes and show them to you in a new way,” Burns says about the plot he can’t disclose. “I would say: There are four really famous actors in this movie and someone gets killed, someone gets [lucky], and someone gets played. And that leaves one other person.”

The four actors are Rooney Mara, Jude Law, Channing Tatum, and Catherine Zeta-Jones. Mara plays a young woman depressed by her husband’s imprisonment for financial shenanigans and the loss of their lifestyle even after he’s released. Tatum is the husband. Zeta-Jones plays Mara’s first psychiatrist, Law her second. He’s the one who prescribes a made-for-the-movie anti-anxiety medication called Ablixa, complete with its own fake website (www.tryablixa.com) and unpleasant side effects. Good things do not happen. Unexpected ones do.

Burns spent almost a decade developing “Side Effects,” his interest in the intersection of psychiatry, pharmacology, and crime piqued by research for the controversial and short-lived TV show “Wonderland,” set in a mental institution. It was at New York’s Bellevue Hospital that Burns befriended Dr. Sasha Bardey, then deputy director of forensic psychiatry, and the two began collaborating on the movie. As he describes it, Burns provided the framework, Bardey the context.

“We’ve all seen more and more ads on TV and there are more drugs and obviously we live in a society where, whether you’re Lance Armstrong or the person at the next table at the restaurant, it’s become quite commonplace to take a pill for one reason or another,” Burns said. “What used to be a reasonable response to a set of events in your life has now become akin to being out of shape. It’s considered really unattractive to be sad or anxious and we don’t do a great job of differentiating between a justified state of sadness and a state of depression.”

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Both Burns and Soderbergh can — and do — speak at length about psychiatry in general and the pharmaceuticals that have become the relatively inexpensive, go-to alternative to the talking cure. Even in separate conversations several days apart, the two exhibit a familiarity based on actual friendship, riffing off each other’s ideas and then advancing them.

Then again, they’ve worked together many times. Burns wrote and Soderbergh directed “Contagion” and “The Informant!” The “Side Effects” collaboration came about when another movie of theirs, “Man From U.N.C.L.E.,” fell apart. Soderbergh, who rose to fame with 1989’s “sex, lies, and videotape,” used that failure as an excuse to ask Burns once again if he’d let Soderbergh oversee his screenplay. Burns finally caved.

“It’s a really elegant way to take an issue, a public issue, a social issue, and sort of wind it into a thriller,” Soderbergh says of Burns’s script. “So I was bugging him about it. I wanted him to give it to me and he wanted to keep it for himself. And so every once in a while, once a year, I’d sort of inquire whether he’d be willing to give it up and he’d say, ‘No I want to hang onto it,’ which I understand.”

Adds Burns, who wrote and directed 2006’s “PU-239,” which Soderbergh produced along with George Clooney, “It was always my plan to direct [‘Side Effects’].” But eventually Soderbergh’s pleas won out. “He has certainly helped me in my career and it was my honor to return the favor. As a screenwriter the goal is to get the movie made. If you’re not going to do it yourself, next best is that an amazing director is going to do it and include you in the process.”

Soderbergh, who won the best director Academy Award for “Traffic,” calls the result serendipity. And he’s seen it before. He was also set to helm “Moneyball,” starring Brad Pitt. But his vision wasn’t the one the studio wanted, and he was left with 150 or so production people needing work. So he did the action-thriller “Haywire” with them instead, and met Tatum. The duo went on to make last year’s “Magic Mike,” a male stripper film with a heart. Another Soderbergh repeat ensemble cast member was born. The group includes Clooney, Law, and Matt Damon, who costars along with Michael Douglas in Soderbergh’s Liberace biopic “Behind the Candelabra,” set to air this spring on HBO.

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Those actors, however, will soon have to find another steady director. Soderbergh swears he is, if not retiring from moviemaking, taking a much-needed hiatus of indeterminate duration.

Jude Law and Catherine Zeta-Jones play a pair of psychiatrists in the new Steven Soderbergh film “Side Effects.” Soderbergh says the film may be the last he directs for quite a while.

‘If I can’t annihilate everything that came before and reemerge as something different, then I won’t come back.’

In a long, wide-ranging conversation that veers from the way technology is rerouting people’s brains to how he tells his almost 22-year-old daughter to handle sexual harassment (strongly, smartly, and, if possible, humorously) to the play about the 1999 Columbine school shootings he plans to direct in New York from another script by Burns, Soderbergh says he’s hit the proverbial wall when it comes to directing films.

“It’s time to reassess and you can’t do that while you’re in it,” he says. “I don’t know what’s going to happen is the real answer. I do know that unless I can come back different, then I won’t come back. If I can’t annihilate everything that came before and reemerge as something different, then I won’t come back. . . . This is something that if you’re going to change, it has to be a complete scorched earth kind of thing, burn it down and see if you can start over.”

Soderbergh, who has a book in the works that he describes as downloading about the job of directing and who plans to auction much of his own movie memorabilia to raise money for a variety of charities, swears he won’t be like Barbra Streisand or the Who, returning to give just one more farewell concert year after year after year. He says his planned retirement isn’t another way to sell tickets to “Side Effects,” honest.

Anyway, he says he doesn’t believe talking to the media makes any difference at all when it comes to selling those tickets because, as he points out, most movies fail regardless. He says he thinks people are already decided about “Side Effects,” and that he can only hope the mystery holds in the interim.

“It’s hard because everybody knows everything now,” he says with a sigh. “I think at least the stuff that’s come out so far about the movie, people have been cool. They recognize we’re screwed if someone decides to tell the whole thing. You’re also screwing with your reader. Why would you want to screw with their experience? So don’t do it. I’d like everyone not to do it.”